oa Editorial [Hot Topic: Astrocytic Signal Transduction in CNS Disease and Therapy (Guest Editor: Liang Peng)]

I am deeply grateful to professors Axel Ullrich and Gyorgy Keri that they trusted me to produce this ‘hot topic’ special issue about ‘Astrocytic Signal Transduction in CNS Disease and Therapy’. I am equally grateful to the nine contributors, not only for their excellent papers, but also for their effort and ability to meet the strict deadline, so that the issue will be timely published, as promised by the Publisher. Finally, a big thank you to the reviewers (Dr. L. Hertz in Canada, Dr. J. De Keyser in Belgium, Dr. Y. Chen in Washington, DC, and my own coworker, Dr. T. Du) for their prompt and thorough reviews, and no less to Dr. B. Li, who has helped me through a myriad of practical problems. 2011 is the one hundred year anniversary of Ramon y Cajal's “Histologie du Systeme Nerveux de l'Homme et des Vertebres”, in which he wisely wrote that the roles of glial cells were unknown and would remain so for a long time, because we did not have the equipment to investigate them. This has changed over the last half century, beginning with the Swedish Holger Hyden's microdissection and protein microanalysis, leading him to realize that astrocytic changes precede neuronal changes in Parkinson's disease, and from there spreading first to other neurochemical investigations, later to a huge burst of activity in studies of glial physiology, and much more slowly to pharmacology. I believe this issue is a ‘first’ in concentrating on signaling pathways involved in neurological, neurosurgical or psychiatric diseases and/or activated by drugs having therapeutic effects under these conditions. Classically, molecular biology has been of greatest importance in cancer therapy, and I am happy to begin the issue with a thoughtful and comprehensive paper by Dr. E.M. Halatsch on problems when targeting the epidermal growth factor receptor in the treatment of glioblastoma and how it may be possible to enhance the effect of such treatment in the future. Astrocytes are also important in multiple sclerosis, and Dr. J. De Keyser has pursued the roles of the loss of specifically β2-adrenergic receptors in white matter astrocytes all the way to the present comprehensive concept, how this loss may account for astrocytic, oligodendrocytic and neuronal deficiencies in MS, and how it might be possible to substitute for the missing noradrenergic receptor by fluoxetine-mediated activation of serotonergic signaling. Immunological disturbances are important not only in MS, but also greatly contribute to Alzheimer's disease and HIV encephalopathy. Drs. Iram and Frenkel elegantly and convincingly describe the enormous influence of astrocytes on β-amyloid deposition and clearance, once again bringing this toxic compound to the forefront of Alzheimer research interest. The huge increase in knowledge about astrocytic signaling in HIV-1 associated encephalopathy during the last few years, including the fascinating, and catastrophic, additive damage by illicit drugs is authoritatively discussed by Dr. V. Buch and her colleagues. Dr. M.D. Norenberg, a pioneer in hepatic encephalopathy and ammonia research, concentrates in his review on the newly established importance of nuclear factor-kappa B (NF-κB) as a major signaling molecule in the pathways eventually leading to brain swelling. My own paper also discusses brain swelling, but in this case induced by elevated K+ concentrations, known to occur during brain trauma, as well as pharmacological means to reduce swelling and provide neuroprotection. Astrocytic signaling in persistent, pathological, as compared to acute, pain has attracted intense interest during the last several years, and this topic is comprehensively reviewed by Dr. F. Wei, including the important involvement of supraspinal brain regions. Based on experiments in cultured astrocytes and astrocytes from fluoxetine-treated anmals, showing delayed depression- and antidepressant-relevant changes in gene expression, editing and function after chronic fluoxetine treatment, Dr. L. Hertz and his co-authors challenge the conventional view that the antidepressant ‘serotonin-specific reuptake inhibitors’ (SSRIs) owe their effects solely to inhibition of the serotonin transporter. Finally, Dr. O. Gonzalez-Perez and his team discusses differences between fibroblast growth factor (FGF), especially FGF2, actions on its receptors in the two major ‘niches’ for adult neurogenesis and oligodendrogenesis, the subventricular zone in the cerebral hemispheres, and the subgranular zone in hippocampus, differences that may become of great practical importance with the impending development of stem cell therapy. Personally, I am stunned by the magnitude of this combined source of information, which exceeds my wildest expectations, when we started this project. I feel this is an indication of the importance of astrocytic signaling in brain diseases, which already has lead to therapeutic advances, and in the future may contribute essentially to the treatment of some of the most devastating brain diseases. I wish the issue will have a wide-spread readership and also believe that each of us can learn from chapters by other authors, especially considering the many similarities in signaling under the various conditions